ProjectSummary/Abstract Theoverarchinggoalsofmyresearcharetofullycharacterizenewfunctionalmagneticresonanceimaging (fMRI)methodsforquantitativephysiologicalimagingtomeetakeyclinicalneed:theabilitytoquantitatively measurebrainactivityandchangesinhumanbrainstatesinbothhealthanddisease.Thisisparticularlyuseful forunderstandingcognitivedeclineinavarietyofdiseasestates.NoninvasivefMRImethodshavethepotential tobeusedasclinicaltoolsforassessingchangesinhumanbrainfunction,suchasafteratherapeutic interventionorprocedure.However,thebloodoxygenationleveldependent(BOLD)signalaloneisdifficultto interpretbecauseofitscomplexity.QuantitativefMRImethodsthatmeasurecerebralbloodflow(CBF)and cerebralmetabolismofoxygen(CMRO2)inboththebaselinestateandinresponsetoastimuluscould potentiallyprovideapowerfulapproachtoovercomingthelimitationsofconventionalBOLD:thechangein CMRO2canbetakenasametricofthechangeinneuralactivity(theenergycostofthatactivity);?therationof fractionalchangesinCBFandCMRO2canbetakenasanindexofneurovascularcoupling;?andbaselineCBF andCMRO2provideacharacterizationofthebaselinestate.Thisproposalseekstoutilizeanalternative approachtomeasuringtheabovemetricsnoninvasively,thusestablishingafoundationforclinicalapplications ofthesetoolsbytestingtheirabilitytoreliablycharacterizeCBFandCMRO2forthebaselinestateand changesassociatedwithcognitivetasks.Aim1willextendtheapplicationofthisnewsuiteoftoolstosub- corticalareasofthebrain(basalganglia)whileformingabridgebetweencognitiveinvestigationsandprevious studiesinthevisualcortex.Resultsfromtheworkwilldeterminereproducibilityandpopulationvariabilityofthe metricsmeasuredwiththequantitativetools.Aim2focusesonahighlycognitivelyrelevantregion,the hippocampus,thatispreviouslyuntestedandmuchmorecomplex.Usingthesetoolstoproperlycharacterize hippocampalactivitywillpavethewayforfuturestudieslookingatmemorydysfunctioninadiseasestate.This proposallaysafoundationforclinicalapplicationsbytestingtheabilityofthenewmethodstocharacterize cognitivebrainfunctioninagroupofhealthyhumansubjects,sothatthetechniquescansubsequentlybeused toinformtreatmentanddiseaseprogressionintheindividualpatient.